Turku PET Centrewttc.triumf.ca/pdf/2004/Sunday pdf/Survival strategies... · 2006-08-08 · 14 May...

14 May 2004 Turku PET Centre/ Olof Solin

Turku PET CentreFinland

A Joint National Research Institute ofUniversity of Turku,

Åbo Akademi University and Turku University Central Hospital


Turku PET Centre • A National Research Institute for PET• Staff and investigators: 98 persons• 3 cyclotrons, 4 PET scanners, 1 MRI (2004)• Facilities about 3000 m2, 16 hot cells (2004)• >30 different tracers in routine use• 80% research, 20% diagnostic service• ~100 publications / year

http://pet.utu.fi


Facilities• Åbo Akademi University

– Cyclotron laboratory 1973• University of Turku

– Radiochemistry laboratory 1978– Medicity preclinical laboratory 1992

• TUCH– PET-laboratory (1. PET Scanner) 1988– O-15 cyclotron 1992

• National PET Centre 1996– 2nd PET Scanner 1996– New PET-Centre building 1999– New radiocemistry laboratory 2003– New cyclotron 2003– New high resolution PET 2003– PET/CT scanner 2004


Turku PET Centre - Key Tasks

• High quality scientific work

• Diagnostic service for the whole country


The Research Strategy of the Turku PET Centre

• Cellular Energy Metabolism in Health andDisease

• Neurotransmission in Health and Disease

• Drug Discovery and Development


Turku PET Centre Functional Organisation

Metabolic ResearchPirjo Nuutila

Neurotransmission ResearchJarmo Hietala

Drug ResearchHarry Scheinin

National scientificboard

Management group Scientific project group

Quality ManagerPertti Lehikoinen

(GMP QA, TUCH PharmacyKirsti Torniainen)

CyclotronsStefan Johansson

AutomationTimo Saarinen

Radionuclide productionSven-Johan Heselius

F-18 ChemistryOlli Eskola

C-11 ChemistryKjell Någren

O-15 ChemistryHannu Sipilä

Laboratory functionNina Lauren

RadiochemistryJörgen Bergman

Preclinical imagingMerja Haaparanta

PET scanningHelena Luotolinna-Lybeck

Modelling and dosimetryVesa Oikonen

Information TechnologyPetri Numminen

ImagingMika Teräs

Diagnostic serviceHeikki Minn

DirectorJuhani Knuuti

Executive Board

Research projects

Radiochemistry ResearchOlof Solin


Turku PET Centre organisation

Management group• Permanent staff

– Isotope production– Radiochemistry/Pharmacy– Imaging– Modelling

Scientific project group• Metabolic research• Neurotransmission res.• Drug research• Targetry / Instrumentation/

Radiochemistry /Modelling


How to do PET?

• Radionuclide production• Substrate labeling (radiochemistry)• Quality control• PET scan• Data analysis

– Blood radioactivity samples, metabolites– Modeling

• Interpretation


What can be studied with PET?

• Tissue blood flow • Tissue metabolism• The function of neurotransmitters and

receptors• Drug pharmacokinetics and –dynamics• Gene expression


[15O] TRACERS

[15O]H2O [15O]water Blood flow

[15O]CO [15O]carbon monoxide Blood volume

[15O]O2 [15O]oxygen Oxygen consumption


[18F] TRACERS

[18F]CFT 2β-carbomethoxy-3β-(4-[18F]fluorophenyl)tropane

Dopamine re-uptake sites in the brain

[18F]FBPA 4-dihydroxyboryl-2-[18F]fluoro-L-phenylalanine

Amino acid transport, boroncarrier for BNCT

[18F]FDG 2-[18F]fluoro-2-deoxy-D-glucose Glucose metabolism

[18F]FDOPA 4,5-dihydroxy-2-[18F]fluoro-L-phenylalanine

Pre-synaptic dopaminergic function in the brain

[18F]FETNIM 4-[18F]fluoro-2,3-dihydroxy-1-(2-nitroimidazol-1-yl)-butanol

Tissue hypoxia

[18F]Fluoride Bone scintigraphy

[18F]Fluorodopa-mine

2-(4,5-dihydroxy-2-[18F]fluorophenyl)ethylamine

Adrenergic innervation and tone in the heart

[18F]Fluorometa-raminol

(1R,2S)-2-amino-1-(4-[18F]fluoro-3-hydroxyphenyl)-1-propanol

Adrenergic innervation in the heart

[18F]FTHA 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid

Fatty acid metabolism


[11C] TRACERS[11C]Acetate Oxidative metabolism in the heart[11C]Carfentanil [methyl-11C]-4-[(1-oxypropyl)phenyl-amino]-1-(2-phenylethyl)-4-

piperidinecarboxylic acid methyl esterOpiate receptors in the brain

[11C]CFT [N-methyl-11C]-2-β-carbomethoxy-3-β--(4-fluorophenyl)-tropane Dopamine re-uptake sites in the brain

[11C]Choline [N-methyl-11C](2-hydroxyethyl) trimethylammonium Choline metabolism, tumours

[11C]CIT [N-methyl-11C]-2-β-carbomethoxy-3-β--(4-iodophenyl)-tropane Dopamine re-uptake sites in the brain

[11C]Deprenyl Monoamine oxidase B in the brain[11C]Dopa Pre-synaptic dopaminergic function in the brain

[11C]FLB 457 [2-O-methyl-11C]-(s)-N-((1-ethyl-2-pyrrolidinyl)-methyl)-5-bromo-2,3-dimethoxybenzamide

Extrastriatal dopamine D2 receptors in the brain

[11C]Flumazenil Benzodiazepine receptors in the brain

[11C]MeAIB α-[11C]methylamino-isobutyric acid System A amino acid transport[11C]Methionine Amino acid transport, tumours[11C]Metomidate O-[methyl-11C]-(R)-1-(1-phenethyl)-1H-imidazole-5-carboxylic

acid methyl ester11β-hydroxylase activity in adrenal cortical tissue

[11C]MHED [11C]m-hydroxyephedrine Adrenergic innervation in the heart[11C]MP4A [methyl-11C]N-methylpiperidyl-4-acetate Acetylcholine esterase activity in the brain

[11C]NMSP [11C]N-methyl-spiperone Dopamine D2 (striatum) and serotonin 5HT2 (extrastriatally) receptors in the brain

[11C]NNC 756 [methyl-11C]-(S)-(+)-8-chloro-5-(2,3-dihydro-benzofuran-7-yl)-7-hydroxy-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine

Dopamine D1 receptors in the brain

[11C]Palmitate Fatty acid metabolism in the heart[11C]Raclopride Striatal dopamine D2 receptors in the brain

[11C]SCH 23390 [methyl-11C]-(R)-(+)-8-chloro-5-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol

Dopamine D1 receptors in the brain

[11C]SCH 39166 [11C]Ecopipam Dopamine D1 receptors in the brain

[11C]WAY 100635 [carbonyl-11C]N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridyl)-cyclohexane- carboxamide

Serotonin 5HT1A receptors in the brain


Turku PET Centre Today• 1400-1800 PET-studies /year• Scientific productivity (1993-2003)

1993 1 Thesis 21 Articles1994 1 Thesis 24 Articles1995 2 Theses 45 Articles1996 2 Theses 33 Articles1997 41 Articles1998 6 Theses 40 Articles1999 6 Theses 56 Articles2000 2 Theses 79 Articles2001 9 Theses 79 Articles2002 4 Theses 82 Articles2003 8 Theses 80 ArticlesTotal 41 Theses 586 Articles

31 theses in progress


Radionuclide productionTargetry and target chemistry


Cyclotron CC-18/9


Light emission during Nitrogenbombardment with protons


Gas target chamber for CC 18/9


Nuclear reactions for 18F

• 20Ne(d,α)18F 20Ne(3He,αn)18Ne 18F

• 16O(α,d)18F 16O(t,n)18F

• 19F(p,d)18F 19F(p,2n)18Ne 18F

• 18O(p,n)18F


Nuclide SAmax [Ci/µmol]

11C 920013N 1880015O 9200018F 1700

3H 0.02914C 0.00006232P 9.1

-- Amount radioactivity/mass [Amount radioactivity/mass [Ci/Ci/µµmolmol]]

-- SA theoretical maximumSA theoretical maximum

SASAmaxmax= N= NAA * ln2 / T* ln2 / T1/21/2

NA = Avogadros number

Specific radioactivity, SA


•Substrate labeling (radiochemistry)


Synthesis of 18F labelled radiopharmaceuticals

PRODUCTION OF 18F

NUCLEOPHILIC 18F ELECTROPHILIC 18F

NUCLEOPHILICLABELLING

ALKYLATIONREAGENTS [18F]FLUOROMETHANE

ALKYLATIONSYNTHESIS OF[18F]F2

ELECTROPHILICLABELLING


Automated radiosynthesis


In vitroIn vitro human brain (100 human brain (100 µµm slices)m slices)A: Incubation with 40 pmol/L [18F]NK-1 tracerB: The same displaced with 1 µmol/L tracer

A.

B.

NK 1 radioligand, in-vitro human brain study


BIOL PSYCHIATRY 2004;55:1007–1012 M. Bergstrom et alPredose (top) and postdose (bottom) PET scans at the level of the cerebellum (left) and striatum (right).

Estimated relationship between plasma concentration of aprepitant and occupancy of striatal NK1 receptors.

NK1 dose/occupancy study


Pharmacokinetics of positron emission tomography (PET) tracers in plasma

Digital autoradiography/ thin layer cromatographyDAR/TLC

Image of radioactivity distribution on TLC plate

Analysis of radioactivity distribution on TLC plateMolecular Imaging and Biology, 6 (2004) 27-33 Haaparanta et al.


4022453388468409423401441372240227200Total1596---------[18F]FDA

2912125--------[18F]FBPA

30--9183------[18F]FETNIM

1362913-314518-----[18F]SPA-RQ

79---13420213---[18F]F-

11221-17--19142219--[18F]FTHA

232-416182844524327--[18F]CFT

66116175961110807079626443[18F]FDOPA

2728366336362280203220284225132163157[18F]FDG

Total20032002200120001999199819971996199519941993

Number of PET studies

Production of Production of 1818FF--tracers during 1993tracers during 1993--20032003

Turku PET Centrewttc.triumf.ca/pdf/2004/Sunday pdf/Survival strategies... · 2006-08-08 · 14 May...

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